| Title | Runx2 (Runt-Related Transcription Factor 2)-Mediated Microcalcification Is a Novel Pathological Characteristic and Potential Mediator of Abdominal Aortic Aneurysm |
| Authors | Li, Zhiqing Zhao, Zuoquan Cai, Zeyu Sun, Yong Li, Li Yao, Fang Yang, Liu Zhou, Yuan Zhu, Haibo Fu, Yi Wang, Li Fang, Wei Chen, Yabing Kong, Wei |
| Affiliation | Peking Univ, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol, Sch Basic Med Sci,Minist Educ, Beijing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Dept Nucl Med, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing 100037, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Cardiovasc Dis, Dept Pathol, Natl Ctr Cardiovasc Dis,Fuwai Hosp, Beijing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Cardiovasc Dis, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Beijing, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Bioact Subst & Funct Nat Med, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Inst Mat Med, Beijing, Peoples R China Univ Alabama Birmingham, Dept Pathol, 1825 Univ Blvd,614 Shelby Biomed Res Bldg, Birmingham, AL 35294 USA Peking Univ, Sch Basic Med Sci, Dept Biomed Informat, Beijing, Peoples R China |
| Keywords | BEAM COMPUTED-TOMOGRAPHY SMOOTH-MUSCLE-CELL II-INFUSED MICE CALCIUM-PHOSPHATE CALCIFICATION INFLAMMATION MACROPHAGES ATHEROSCLEROSIS RUPTURE VOLUME |
| Issue Date | May-2020 |
| Publisher | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY |
| Abstract | Objective: Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification, as detected by fluorine-18-sodium fluoride, has recently been recognized as a valuable indicator in predicting atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification involved in the pathogenesis of AAA remains elusive. Approach and Results: Microcalcification was analyzed in human aneurysmal aortas histologically and in AngII (angiotensin II)-infused ApoE(-/-) mouse aortas by fluorine-18-sodium fluoride positron emission tomography and X-ray computed tomography scanning in chronological order in live animals. AAA patients' aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared with non-AAA patients. Enhanced fluorine-18-sodium fluoride uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo. RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII-infused ApoE(-/-) mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 (runt-related transcription factor 2) in AAA. Consistently, vascular smooth muscle cell-specific Runx2 deficiency markedly repressed AngII-induced AAA formation in the ApoE(-/-) mice compared with the control littermates. Conclusions: Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment. |
| URI | http://hdl.handle.net/20.500.11897/588626 |
| ISSN | 1079-5642 |
| DOI | 10.1161/ATVBAHA.119.314113 |
| Indexed | SCI(E) Scopus |
| Appears in Collections: | 分子心血管学教育部重点实验室 基础医学院 |
